1α,25-Dihydroxyvitamin D3 and 24R,25-Dihydroxyvitamin D3 Modulate Growth Plate Chondrocyte Physiology via Protein Kinase C-Dependent Phosphorylation of Extracellular Signal-Regulated Kinase 1/2 Mitogen-Activated Protein Kinase
| Autor: | Zvi Schwartz, D. Larsson, Barbara D. Boyan, D. Lopez, V. Bingham, David D Dean, H. Ehland, R. R. Hardin, Victor L. Sylvia |
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| Rok vydání: | 2002 |
| Předmět: |
Male
24 25-Dihydroxyvitamin D 3 Blotting Western Mitogen-activated protein kinase kinase Gene Expression Regulation Enzymologic MAP2K7 Rats Sprague-Dawley Chondrocytes Endocrinology Calcitriol Animals ASK1 Growth Plate RNA Messenger Phosphorylation Protein kinase A signaling Cells Cultured Protein Kinase C Protein kinase C MAP kinase kinase kinase biology Cyclin-dependent kinase 2 Alkaline Phosphatase Blotting Northern Molecular biology Rats Cell biology Enzyme Activation Phospholipases Prostaglandin-Endoperoxide Synthases biology.protein Indicators and Reagents Proteoglycans Cyclin-dependent kinase 9 Mitogen-Activated Protein Kinases Signal Transduction |
| Zdroj: | Endocrinology. 143:2775-2786 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endo.143.7.8889 |
| Popis: | Membrane-mediated increases in protein kinase C (PKC) activity and PKC-dependent physiological responses of growth plate chondrocytes to vitamin D metabolites depend on the state of endochondral maturation; 1alpha,25-dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)] regulates growth zone (GC) cells, whereas 24R,25-(OH)(2)D(3) regulates resting zone (RC) cells. Different mechanisms, including protein kinase A signaling, mediate the effects of 1alpha,25-(OH)(2)D(3) and 24R,25-(OH)(2)D(3) on PKC, suggesting that different mechanisms may also regulate any MAPK involvement in the physiological responses. This study used confluent cultures of rat costochondral chondrocytes as a model. 1alpha,25-(OH)(2)D(3) stimulated MAPK specific activity in GC in a time- and dose-dependent manner, evident within 9 min. 24R,25-(OH)(2)D(3) stimulated MAPK in RC; increases were dose dependent, occurred after 9 min, and were greatest at 90 min. In both cells the effect was due to ERK1/2 activation (p42p44 in GC; p42 = p44 in RC). MAPK activation was dependent on PKC, but not protein kinase A. The effect of 1alpha,25-(OH)(2)D(3) required phospholipase C, and the effect of 24R,25-(OH)(2)D(3) required phospholipase D. Inhibition of cyclooxygenase activity reduced the effect of 1alpha,25-(OH)(2)D(3) on MAPK in GC and enhanced the effect of 24R,25-(OH)(2)D(3) in RC. Based on MAPK inhibition with PD98059, ERK1/2 MAPK mediated the effect of 24R,25-(OH)(2)D(3) on [(3)H]thymidine incorporation and [(35)S]sulfate incorporation by RC, but only partially mediated the effect of 1alpha,25-(OH)(2)D(3) on GC. ERK1/2 was not involved in the regulation of alkaline phosphatase specific activity by either metabolite. This paper supports the hypothesis that 1alpha,25-(OH)(2)D(3) regulates the physiology of GC via rapid membrane-mediated signaling pathways, and some, but not all, of the response to 1alpha,25-(OH)(2)D(3) is via the ERK family of MAPKs. In contrast, 24R,25-(OH)(2)D(3) exerts its effects on RC via PKC-dependent MAPK. Whereas 1alpha,25-(OH)(2)D(3) increases MAPK activity via phospholipase C and increased prostaglandin production, 24R,25-(OH)(2)D(3) increases MAPK via phospholipase D and decreased prostaglandin production. The cell specificity, metabolite stereospecificity, and the dependence on PKC argue for the participation of membrane receptors for 1alpha,25-(OH)(2)D(3) and 24R,25-(OH)(2)D(3) in the regulation of ERK1/2 in the growth plate. |
| Databáze: | OpenAIRE |
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